A Multicenter, Single Arm, Open Label, Pilot Study to Assess the Effect of Atrasentan Alongside Supportive Care on Structural and Functional Changes in Kidneys of Adult Patients With IgA Nephropathy (IgAN)
| Registry | NCT07820995, acronym A-MECH |
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| Status | Not yet recruiting |
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| Phase | Phase 4 |
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| Study type | Interventional; na, single group, masking: none, treatment |
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| Enrollment | 20 (Estimated) |
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| Sponsor | University of Illinois at Chicago (Other); collaborators: Novartis, University of Michigan, Endeavor Health, University of North Carolina, Chapel Hill, Icahn School of Medicine at Mount Sinai |
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| Conditions | IgA Nephropathy (IgAN), Immunoglobulin A Nephropathy (IgAN) |
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| Interventions | atrasentan (Drug) |
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| Dates | start 2026-09-29 (estimated), primary completion 2027-12-31 (estimated), completion 2028-12-31 (estimated), first posted 2026-09-15, last updated 2026-09-21 |
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| Locations | 1 site in United States |
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Related Papers Related Patents Related Grants Related Experts
All trials for IgA Nephropathy (IgAN) All trials for Immunoglobulin A Nephropathy (IgAN) All trials of atrasentan
-Summary
This multicenter, single-arm, open-label Phase 4 pilot study evaluates the effects of atrasentan added to optimized supportive care on kidney structure and function in adults with biopsy-confirmed IgA nephropathy. Approximately 20 participants will receive atrasentan 0.75 mg orally once daily for 52 weeks. Kidney multiparametric MRI is performed at baseline, 6 months, and 12 months, with blood and urine biomarker assessments throughout treatment. An optional nested cohort of up to 5 participants undergoes native kidney biopsy at baseline and 12 months.
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+Arms and interventions
| Arm | Type | Interventions | Description |
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| Atrasentan | Experimental | Drug: atrasentan | Adults with biopsy-confirmed IgAN receive atrasentan 0.75 mg orally once daily for 52 weeks in addition to optimized supportive care. The optional repeat-biopsy cohort is nested within this arm and is not a separate randomized arm. |
- atrasentan (Drug), also known as vanrafia: Atrasentan 0.75 mg oral tablet once daily for 52 weeks, added to optimized supportive care.
+Outcome measures
Primary outcomes
- Proportion of participants achieving improvement in at least one component of the composite kidney mpMRI endpoint at Month 6 [Baseline to Month 6 (Week 26)]: The proportion of participants with improvement from baseline at Month 6 in at least one of: ≥5% decrease in cortical native T1 mapping time; ≥5% increase in cortical apparent diffusion coefficient (ADC); or ≥10% increase in phase-contrast-derived renal artery blood flow.
Secondary outcomes
- Percent change from baseline in urinary KIM-1 and MCP-1 over 6 months [Baseline through Month 6]: Percent change from baseline in urine biomarkers Kidney Injury Molecule-1 (KIM-1) and Monocyte Chemoattractant Protein-1 (MCP-1), assessed individually and/or as a composite.
Other outcomes
- Composite kidney mpMRI endpoint at Month 12 [Baseline to month 12]: Change from baseline in composite and individual imaging biomarkers; Month 12.
- Imaging biomarker trajectory over 12 months [Baseline to month 12]: Geometric mean percent change from baseline in composite and individual imaging biomarkers at Month 6 and Month 12.
- Urine and blood biomarkers over 12 months [Baseline to month 12]: Geometric mean percent change from baseline at Weeks 4, 12, 26 and 52.
- Imaging biomarker slopes [baseline to Month 12]: Change over time from baseline to Month 12 in T1 mapping, ADC and phase-contrast renal artery blood flow.
- Urine/blood biomarker slopes [Baseline to Month 12]: Change over time from baseline to Month 12 in composite and individual biomarkers.
- Histopathology in biopsy cohort [Baseline to Month 12]: Change from baseline to Month 12 in MEST-C scoring and histopathologic staining in the nested repeat-biopsy cohort.
- Tissue expression profiles in biopsy cohort [Baseline to Month 12]: Change from baseline to Month 12 in regional proteomics, transcriptomics and single-cell/nucleus RNA sequencing expression profiles.
- Correlation with clinical kidney measures [Baseline to month 12]: Correlation of changes in UPCR and eGFR with imaging and biochemical biomarker outcomes.
+Eligibility
Sex: All, ages: 18 Years to any
Inclusion Criteria:
1. Signed informed consent.
2. Male or female ≥18 years with biopsy-confirmed IgAN; eGFR ≥30 mL/min/1.73 m² for main cohort; >40 mL/min/1.73 m² for optional biopsy cohort.
3. Screening UPCR ≥0.5 g/g measured by first morning void.
4. Maximally tolerated or locally approved maximal ACEi/ARB dose before enrollment; diuretics, other antihypertensives and SGLT2i, if used, stabilized for at least 90 days before baseline.
5. WOCBP and sexually active participants must comply with protocol contraception requirements.
Exclusion Criteria:
1. Hypersensitivity to study treatment/excipients or similar drug classes.
2. CKD primarily attributable to non-IgAN etiology.
3. Suspected RPGN or IgA vasculitis.
4. Nephrotic syndrome.
5. BNP >200 pg/mL or NT-proBNP >450 pg/mL at screening.
6. Platelets <80,000/µL.
7. Organ transplant history other than corneal transplant.
8. Systemic immunosuppressants >2 weeks in prior 3 months or rituximab within 6 months.
9. Confirmed BP >150/95 mmHg based on mean of 3 screening measurements.
10. Heart failure/fluid overload.
11. Significant liver disease or transaminases/bilirubin >2× ULN.
12. Hemoglobin <9 g/dL or transfusion for anemia within 3 months.
13. Malignancy unless protocol-defined exception.
14. Pregnancy/breastfeeding or intent to become pregnant.
15. Male intent to father a child/donate sperm during study and 1 month after.
16. Recent investigational/approved IgAN treatment per protocol washout.
17. Clinically significant unstable/uncontrolled medical disorder that may confound results or add risk.
18. Alcohol/illicit drug-related disorder within 3 years.
19. WOCBP not using highly effective contraception; sexually active males unwilling to use condoms.
20. Prohibited therapies.
21. MRI contraindications.
22. Optional biopsy cohort exclusion if biopsy risk is unacceptably high.
+Locations (1)
| Facility | City | Country | Status |
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| University of Illinois Chicago | Chicago, Illinois | United States | |
+Publications
- Kidney Disease: Improving Global Outcomes (KDIGO) IgAV Work Group. (2025). KDIGO 2025 clinical practice guideline for the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV). Kidney International, 108(4), S1-S71. Kohan, D. E., Barratt, J., Heerspink, H. J., Campbell, K. N., Camargo, M., Ogbaa, I., ... & King, A. (2023). Targeting the endothelin A receptor in IgA nephropathy. Kidney International Reports, 8(11), 2198-2210. Kuo, J. J., Wu, J., Gunawan, M. G., McConnell, M. T., Lester, J., Naidu, N. A., ... & Cox, J. H. (2025). Effects of Atrasentan on Kidney Gene Transcription, Mesangial Cell Proliferation, and Proteinuria in Immunoglobulin A Nephropathy. Kidney360, 10-34067. Lai KN, Tang SCW, Schena FP, et al (2016) IgA nephropathy. Nat Rev Dis Primers 2:16001. Lim, R. S., Yeo, S. C., Barratt, J., & Rizk, D. V. (2024). An update on current therapeutic options in IgA nephropathy. Journal of Clinical Medicine, 13(4), 947. Noronha, I. L., Barratt, J., Gorriz, J. L., Kotwal, S., Lim, S. K., Beckett, V., ... & Heerspink, H. J. (2024). WCN24-1868 ASSIST: A randomized double-blind, placebo controlled crossover trial of atrasentan in patients with IgA nephropathy (IgAN) on SGLT2i. Kidney International Reports, 9(4), S178. Peters, H. P. E., Waanders, F., Meijer, E., van den Brand, J. A. J. G., Steenbergen, E. J., van Goor, H., & Wetzels, J. F. M. (2011). High urinary excretion of kidney injury molecule-1 is an independent predictor of end-stage renal disease in patients with IgA nephropathy. Nephrology Dialysis Transplantation, 26(11), 3581-3588. Suzuki Y, Monteiro RC, Coppo R, et al (2021) The Phenotypic Difference of IgA Nephropathy and its Race/Gender-dependent Molecular Mechanisms. Kidney360; 2(8):1339- 1348. Torres, D. D., Rossini, M., Manno, C., Mattace-Raso, F. U. S., D'Altri, C., Ranieri, E., Pontrelli, P., Grandaliano, G., & Schena, F. P. (2008). The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine p
- Barratt, J., Kim, S. G., Inker, L. A., Packham, D. K., Ranganathan, D., Rheault, M. N., ... & Han, S. H. (2025). WCN25-778 AFFINITY study: 1-year results of atrasentan in IgA nephropathy (IgAN). Kidney International Reports, 10(2), S183. Boels, M. G., Avramut, M. C., Koudijs, A., Dane, M. J., Lee, D. H., Van Der Vlag, J., ... & Rabelink, T. J. (2016). Atrasentan reduces albuminuria by restoring the glomerular endothelial glycocalyx barrier in diabetic nephropathy. Diabetes, 65(8), 2429-2439. Buchanan, C.E.; Mahmoud, H.; Cox, E.F.; Prestwich, B.L.; Noble, R.A.; Selby, N.M.; Taal, M.W.; Francis, S.T. Multiparametric Renal Magnetic Resonance Imaging for Prediction and Annual Monitoring of the Progression of Chronic Kidney Disease over Two Years. J. Clin. Med. 2023, 12, 7282. Francis, S. T., Selby, N. M., and Taal, M. W. Magnetic Resonance Imaging to Evaluate Kidney Structure, Function, and Pathology: Moving Toward Clinical Application Am J Kidney Dis. 82(4):491-504. Heerspink, H. J., Jardine, M., Kohan, D. E., Lafayette, R. A., Levin, A., Liew, A., ... & Renfurm, R. (2025). Atrasentan in patients with IgA nephropathy. N Engl J Med, 392(6), 544-554. Heerspink, H. J., Kohan, D. E., & de Zeeuw, D. (2021). New insights from SONAR indicate adding sodium glucose co-transporter 2 inhibitors to an endothelin receptor antagonist mitigates fluid retention and enhances albuminuria reduction. Kidney International, 99(2), 346-349. Heerspink, H. J. Noronha, I. L, Górriz, J. L., Lim, S. K., Kotwal, Sradha S.,…&; Mottl, A. K. . (2026). Efficacy and Safety of Atrasentan in Patients with IgA Nephropathy Receiving Sodium-Glucose Cotransporter 2 Inhibitors: Placebo-Controlled, Crossover Trial. JASN. Heerspink, H. J., Parving, H. H., Andress, D. L., Bakris, G., Correa-Rotter, R., Hou, F. F., ... & Bieler, T. (2019). Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. The Lancet, 393(10184),
+Investigators